Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Organic Chemistry, 7th Edition L. G. Wade, Jr. Chapter 18 Ketones and Aldehydes Copyright © 2010 Pearson Education, Inc. Carbonyl Compounds Chapter 18 2 Carbonyl Structure Carbon is sp2 hybridized. C═O bond is shorter, stronger, and more polar than C═C bond in alkenes. Chapter 18 3 Ketone Nomenclature 1 CH3 O 3 4 C CH CH3 2 CH3 3-methyl-2-butanone 1 CH3 O 3 4 C CH CH2OH 2 CH 3 4-hydroxy-3-methyl-2-butanone Number the chain so that carbonyl carbon has the lowest number. Replace the alkane -e with -one. Chapter 18 4 Ketone Nomenclature (Continued) 1 O 3-bromocyclohexanone 3 Br For cyclic ketones, the carbonyl carbon is assigned the number 1. Chapter 18 5 Aldehydes Nomenclature 5 CH3 CH3 CH2 2 CH CH2 3 O C H 1 3-methylpentanal The aldehyde carbon is number 1. IUPAC: Replace -e with -al. Chapter 18 6 Carbonyl as Substituent On a molecule with a higher priority functional group, a ketone is an oxo and an aldehyde is a formyl group. Aldehydes have a higher priority than ketones. 1 COOH CH3 O CH3 O C CH CH2 C H 4 3 1 3-methyl-4-oxopentanal 3 CHO 3-formylbenzoic acid Chapter 18 7 Common Names for Ketones Named as alkyl attachments to —C═O. Use Greek letters instead of numbers. O O CH3 CH3CH C CH CH3 C CH CH3 Br CH3 methyl isopropyl ketone CH3 a-bromoethyl isopropyl ketone Chapter 18 8 Historical Common Names O C O CH3 CH3 C CH3 acetophenone acetone O C benzophenone Chapter 18 9 Boiling Points Ketones and aldehydes are more polar, so they have a higher boiling point than comparable alkanes or ethers. They cannot hydrogen-bond to each other, so their boiling point is lower than comparable alcohol. Chapter 18 10 Solubility of Ketones and Aldehydes Good solvent for alcohols. Lone pair of electrons on oxygen of carbonyl can accept a hydrogen bond from O—H or N—H. Acetone and acetaldehyde are Chapter 18 miscible in water. 11 Formaldehyde H H H O C H C O O C H O H heat H C H H2O formaldehyde, b.p. -21C HO OH H C H formalin trioxane, m.p. 62C Gas at room temperature. Formalin is a 40% aqueous solution. Chapter 18 12 Infrared (IR) Spectroscopy Very strong C═O stretch around 1710 cm-1. Additional C—H stretches for aldehyde: Two absorptions at 2710 cm-1 and 2810 cm-1. Chapter 18 13 IR Spectra Conjugation lowers the carbonyl stretching frequencies to about 1685 cm-1. Rings that have ring strain have higher C═O frequencies. Chapter 18 14 Proton NMR Spectra Aldehyde protons normally absorb between d9 and d 10. Protons of the α-carbon usually absorb between d 2.1 and d 2.4 if there are no other electron-withdrawing groups nearby. Chapter 18 15 1H NMR Spectroscopy Protons closer to the carbonyl group are more deshielded. Chapter 18 16 Carbon NMR Spectra of Ketones The spin-decoupled carbon NMR spectrum of 2heptanone shows the carbonyl carbon at 208 ppm and the α carbon at 30 ppm (methyl) and 44 ppm (methylene). Chapter 18 17 Mass Spectrometry (MS) Chapter 18 18 MS for Butyraldehyde Chapter 18 19 McLafferty Rearrangement The net result of this rearrangement is the breaking of the α, β bond, and the transfer of a proton from the carbon to the oxygen. An alkene is formed as a product of this rearrangement through the tautomerization of the enol. Chapter 18 20 Ultraviolet Spectra of Conjugated Carbonyl Compounds Conjugated carbonyl compounds have characteristic -* absorption in the UV spectrum. An additional conjugated C═C increases max about 30 nm; an additional alkyl group increases it about 10 nm. Chapter 18 21 Electronic Transitions of the C═O Small molar absorptivity. “Forbidden” transition occurs less frequently. Chapter 18 22 Industrial Importance Acetone and methyl ethyl ketone are important solvents. Formaldehyde is used in polymers like Bakelite. Flavorings and additives like vanilla, cinnamon, and artificial butter. Chapter 18 23 Chapter 18 24 Oxidation of Secondary Alcohols to Ketones Secondary alcohols are readily oxidized to ketones with sodium dichromate (Na2Cr2O7) in sulfuric acid or by potassium permanganate (KMnO4). Chapter 18 25 Oxidation of Primary Alcohols to Aldehydes Pyridinium chlorochromate (PCC) is selectively used to oxidize primary alcohols to aldehydes. Chapter 18 26 Ozonolysis of Alkenes The double bond is oxidatively cleaved by ozone followed by reduction. Ketones and aldehydes can be isolated as products. Chapter 18 27 Friedel–Crafts Reaction Reaction between an acyl halide and an aromatic ring will produce a ketone. Chapter 18 28 Hydration of Alkynes The initial product of Markovnikov hydration is an enol, which quickly tautomerizes to its keto form. Internal alkynes can be hydrated, but mixtures of ketones often result. Chapter 18 29 Hydroboration–Oxidation of Alkynes Hydroboration–oxidation of an alkyne gives anti-Markovnikov addition of water across the triple bond. Chapter 18 30 Solved Problem 1 Show how you would synthesize each compound from starting materials containing no more than six carbon atoms. (a) (b) Solution (a) This compound is a ketone with 12 carbon atoms. The carbon skeleton might be assembled from two six-carbon fragments using a Grignard reaction, which gives an alcohol that is easily oxidized to the target compound. Chapter 18 31 Solved Problem 1 (Continued) Solution (Continued) An alternative route to the target compound involves Friedel–Crafts acylation. (b) This compound is an aldehyde with eight carbon atoms. An aldehyde might come from oxidation of an alcohol (possibly a Grignard product) or hydroboration of an alkyne. If we use a Grignard, the restriction to six-carbon starting materials means we need to add two carbons to a methylcyclopentyl fragment, ending in a primary alcohol. Grignard addition to an epoxide does this. Chapter 18 32 Solved Problem 1 (Continued) Solution (Continued) Alternatively, we could construct the carbon skeleton using acetylene as the two-carbon fragment. The resulting terminal alkyne undergoes hydroboration to the correct aldehyde. Chapter 18 33 Synthesis of Ketones and Aldehydes Using 1,3-Dithianes 1,3-Dithiane can be deprotonated by strong bases such as n-butyllithium. The resulting carbanion is stabilized by the electron-withdrawing effects of two polarizable sulfur atoms. Chapter 18 34 Alkylation of 1,3-Dithiane Alkylation of the dithiane anion by a primary alkyl halide or a tosylate gives a thioacetal that can be hydrolyzed into the aldehyde by using an acidic solution of mercuric chloride. Chapter 18 35 Ketones from 1,3-Dithiane The thioacetal can be isolated and deprotonated. Alkylation and hydrolysis will produce a ketone. Chapter 18 36 Synthesis of Ketones from Carboxylic Acids Organolithiums will attack the lithium salts of carboxylate anions to give dianions. Protonation of the dianion forms the hydrate of a ketone, which quickly loses water to give the ketone. Chapter 18 37 Ketones from Nitriles A Grignard or organolithium reagent can attack the carbon of the nitrile. The imine is then hydrolyzed to form a ketone. Chapter 18 38 Aldehydes from Acid Chlorides Lithium aluminum tri(t-butoxy)hydride is a milder reducing agent that reacts faster with acid chlorides than with aldehydes. Chapter 18 39 Lithium Dialkyl Cuprate Reagents A lithium dialkylcuprate (Gilman reagent) will transfer one of its alkyl groups to the acid chloride. Chapter 18 40 Nucleophilic Addition A strong nucleophile attacks the carbonyl carbon, forming an alkoxide ion that is then protonated. Aldehydes are more reactive than ketones. Chapter 18 41 The Wittig Reaction The Wittig reaction converts the carbonyl group into a new C═C double bond where no bond existed before. A phosphorus ylide is used as the nucleophile in the reaction. Chapter 18 42 Preparation of Phosphorus Ylides Prepared from triphenylphosphine and an unhindered alkyl halide. Butyllithium then abstracts a hydrogen from the carbon attached to phosphorus. Chapter 18 43 Mechanism of the Wittig Reaction Betaine formation Oxaphosphetane formation Chapter 18 44 Mechanism for Wittig The oxaphosphetane will collapse, forming carbonyl (ketone or aldehyde) and a molecule of triphenyl phosphine oxide. Chapter 18 45 Solved Problem 2 Show how you would use a Wittig reaction to synthesize 1-phenyl-1,3-butadiene. Chapter 18 46 Solved Problem 2 (Continued) Solution (Continued) This molecule has two double bonds that might be formed by Wittig reactions. The central double bond could be formed in either of two ways. Both of these syntheses will probably work, and both will produce a mixture of cis and trans isomers. You should complete this solution by drawing out the syntheses indicated by this analysis (Problem 18-16). Chapter 18 47 Hydration of Ketones and Aldehydes In an aqueous solution, a ketone or an aldehyde is in equilibrium with its hydrate, a geminal diol. With ketones, the equilibrium favors the unhydrated keto form (carbonyl). Chapter 18 48 Mechanism of Hydration of Ketones and Aldehydes Hydration occurs through the nucleophilic addition mechanism, with water (in acid) or hydroxide (in base) serving as the nucleophile. Chapter 18 49 Cyanohydrin Formation The mechanism is a base-catalyzed nucleophilic addition: Attack by cyanide ion on the carbonyl group, followed by protonation of the intermediate. HCN is highly toxic. Chapter 18 50 Formation of Imines Ammonia or a primary amine reacts with a ketone or an aldehyde to form an imine. Imines are nitrogen analogues of ketones and aldehydes with a C═N bond in place of the carbonyl group. Optimum pH is around 4.5 Chapter 18 51 Mechanism of Imine Formation Acid-catalyzed addition of the amine to the carbonyl compound group. Acid-catalyzed dehydration. Chapter 18 52 Other Condensations with Amines Chapter 18 53 Formation of Acetals Chapter 18 54 Mechanism for Hemiacetal Formation Must be acid-catalyzed. Adding H+ to carbonyl makes it more reactive with weak nucleophile, ROH. Chapter 18 55 Acetal Formation Chapter 18 56 Cyclic Acetals Addition of a diol produces a cyclic acetal. The reaction is reversible. This reaction is used in synthesis to protect carbonyls from reaction Chapter 18 57 Acetals as Protecting Groups O O HO H O OH H + H O O Hydrolyze easily in acid; stable in base. Aldehydes are more reactive than ketones. Chapter 18 58 Reaction and Deprotection O O O H 1) NaBH4 2) H3O+ H OH O The acetal will not react with NaBH4, so only the ketone will get reduced. Hydrolysis conditions will protonate the alcohol and remove the acetal to restore the aldehyde. Chapter 18 59 Oxidation of Aldehydes Aldehydes are easily oxidized to carboxylic acids. Chapter 18 60 Reduction Reagents Sodium borohydride, NaBH4, can reduce ketones to secondary alcohols and aldehydes to primary alcohols. Lithium aluminum hydride, LiAlH4, is a powerful reducing agent, so it can also reduce carboxylic acids and their derivatives. Hydrogenation with a catalyst can reduce the carbonyl, but it will also reduce any double or triple bonds present in the molecule. Chapter 18 61 Sodium Borohydride OH O R R(H) NaBH4 CH3OH aldehyde or ketone R H R(H) • NaBH4 can reduce ketones and aldehydes, but not esters, carboxylic acids, acyl chlorides, or amides. Chapter 18 62 Lithium Aluminum Hydride OH O R R(H) LiAlH4 ether R H R(H) aldehyde or ketone LiAlH4 can reduce any carbonyl because it is a very strong reducing agent. Difficult to handle. Chapter 18 63 Catalytic Hydrogenation OH O H2 Raney Ni Widely used in industry. Raney nickel is finely divided Ni powder saturated with hydrogen gas. It will attack the alkene first, then the carbonyl. Chapter 18 64 Deoxygenation of Ketones and Aldehydes The Clemmensen reduction or the Wolff– Kishner reduction can be used to deoxygenate ketones and aldehydes. Chapter 18 65 Clemmensen Reduction O C CH2CH3 Zn(Hg) CH2CH2CH3 HCl, H2O O CH2 C Zn(Hg) H CH2 CH3 HCl, H2O Chapter 18 66 Wolff–Kishner Reduction Forms hydrazone, then heat with strong base like KOH or potassium tert-butoxide. Use a high-boiling solvent: ethylene glycol, diethylene glycol, or DMSO. A molecule of nitrogen is lost in the last steps of the reaction. Chapter 18 67